KR900007314B1 - Process for preparing n-(methoxyacetyl)-n-(2,l-dimethyl phenyl)-o-amino-oxazolidine-2-one - Google Patents

Abstract

Prepn. of N-(methoxyacetyl)-N-(2,6-dimethylphenyl)-3- aminooxazolidine-2-one of formula (I), useful as a fungicide, comprises (a) reacting 2,6-dimethylphenyl hydrazine with XCOR to form formula (II); (b) reacting formula (II) with methoxyacetyl chloride to form formula (III); and (c) reacting (III) with ethylene oxide at 50-40 deg.C for 1-5 hrs.

Description

            N- (methoxyacetyl) -N- (2,6-dimethylphenyl) -3-amino-oxazolidine         

Production method of 2-one

The present invention is a novel method of N- (methoxyacetyl) -N- (2,6-dimethylphenyl) -3-amino-oxazolidin-2-one represented by the following structural formula (I) useful as an orchard horticultural fungicide.                 It relates to a manufacturing method.

Known methods for producing a compound represented by the above formula (I) are Romanian Patent No. 81676, British Patent No. 2106907, French Patent No.                 2463132, European Patent No. 30923, West German Patent No. 3033161, West German Patent No. 3030026, and the like,                 Manufacturing methods can be summarized in the following three ways.

[First Method]

The first method is, for example, the production method described in Romania Patent No. 81,676, wherein 2,6-dimethyl phenylhydrazine and bromoethyl represented by the following structural formula (II)                 Chloroformate is reacted with pyridine and benzene to obtain a compound represented by the following structural formula (A), which is reacted with methoxy acetylchloride to                 It is a method of manufacturing the compound represented by structural formula (I).

This method is represented by the following scheme.

[Second method]

The second method is, for example, a manufacturing method described in French Patent No. 2,463,132 (similar to West German Patent No. 3030026), which is represented by the following structural formula (II):                 The compound is reacted with chloroethyl chloroformate at 0 ° C. to 5 ° C. using pyridine to obtain a compound represented by the following structural formula (B), which is added to methoxy acetic                 The anhydride was reacted at 80 ° C. to obtain a compound represented by the following structural formula (C), and then sodium hydride and toluene were used to prepare the compound of the structural formula (I).                 It is a method of manufacturing.

This method is represented by the following scheme.

[Third method]

The third method is, for example, a manufacturing method described in German Patent No. 3,033,161, wherein the compound of formula (II) and bromoethyl chloroformate are substituted with pyridine and benzene.                 To a compound of the following structural formula (B), which was then reacted with tetramethyl guanidine and toluene to obtain a compound of the following structural formula (A).                 Thereafter, methoxy acetyl chloride is reacted with a small amount of N, N-dimethylformamide to prepare a compound of formula (I).

This method is represented by the following scheme.

However, when the compound represented by Structural Formula (I) is prepared by the conventional production method summarized by the above three methods, all are finally obtained.                 The yield of the target compound is low, the reagent used is expensive, and it has big defects such as the use of a difficult compound such as sodium hydride.                 there was.

Therefore, the present inventors have continued a long research to solve the problems of the conventional method as described above, as a result, a new and simple process to produce the target compound in a high yield                 I developed a way to do it.

The present invention is made simple by using ethylene oxide during the reaction in preparing the compound represented by the above formula (I) from 2,6-dimethylphenyl hydrazine.                 The purpose is to provide a method for preparing the target compound in high yield.

Hereinafter, the present invention will be described in detail.

In the present invention, in preparing the compound represented by the structural formula (I), 2,6-dimethylphenyl hydrazine represented by the following structural formula (II) to the following structural formula (III)                 A compound represented by the following structural formula (IV) is prepared by reacting with a compound represented by the following formula, and then reacted with methoxyacetyl chloride to obtain a compound represented by the following structural formula (V).                 A compound was prepared and N- (methoxyacetyl) -N- (2,6-dimethyl represented by Structural Formula (I) above was reacted with ethylene oxide.                 It is characterized by producing phenyl) -3-amino-oxazolidin-2-one.

In the formulas, X represents a halogen atom, R represents a lower alkoxy group or halogen atom of 1 to 5 carbon atoms.

Referring to the present invention in more detail as follows.

In the present invention, in the preparation of the compound of formula (I), first of the 2,6-dimethylphenylhydrazine represented by the formula (II) and the formula (III)                 The compound is reacted, which is carried out in the presence of a suitable base and a solvent, wherein the reaction temperature is 1 to 50 while maintaining a temperature of -10 ° C to 50 ° C.                 It is preferable to react for 2 hours.

The compound of formula IV prepared in this way is reacted with methoxyacetyl chloride in the presence of a suitable base and a solvent to react the compound of formula V.                 To prepare, the reaction at this time is reacted for 1 to 2 hours in the temperature range of -10 ℃ to 50 ℃.

Next, the compound of formula (V) thus prepared is reacted with ethylene oxide in the presence of a suitable base or neutral salt and a solvent to obtain the final compound.                 To prepare a compound represented by the formula (I), the reaction is to react for 1 hour to 5 hours in the temperature range of 50 ℃ to 140 ℃                 good.

Such a preparation method according to the present invention is a completely different method from the conventional method, and in particular, ethylene is added to the compound of the above formula (V) which is a reaction intermediate in the present invention.                 The most characteristic feature is to prepare a compound of formula (I) as a target compound by reacting with an oxide.

In particular, the preparation method of the present invention may be used by separately separating and purifying the compounds of formulas (IV) and (V) as intermediates in the reaction with ethylene oxide, which is the final step.                 It is possible to carry out a continuous reaction with or without separation purification.

Examples of the base used in the method of the present invention as described above include inorganic bases such as sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium carbonate and the like, such as pyridine and triethylamine, etc.                 Organic bases may be used, and neutral salts may be sodium fluoride or potassium fluoride and supported materials such as alumina, celite or silica gel.                 It can be used by injection.

In addition, as the solvent used in the present invention, aromatic hydrocarbons such as benzene, toluene, xylene, chloroform, methylene chloride, ethyl acetate, tetrahydrofuran,                 Acetonitrile, N, N-dimethylformide, N, N-dimethylsulfoxide and the like can be used.

Hereinafter, the present invention will be described in more detail with reference to the following Examples, but the scope of the present invention is not limited by the Examples.

Example 1

Preparation of Methyl 2- (2,6-dimethylphenyl) -hydrazine-carboxylate (compound of formula IV)

2,6-dimethylphenylhydrazine (3 g, 0.022 mole) and potassium carbonate (4.57 g, 0.033 mole) were added to 30 m1 of acetonitrile and maintained at 0 ° C. for 30 minutes.                 Stirred. Methyl chloroformate (2.19 g, 0.023 mol) is added thereto, and the reaction is completed by stirring at 0 ° C to 25 ° C for 1 hour. Then the reactants                 After filtration, the filtrate was removed under reduced pressure, and then 100 ml of ethyl acetate was added, twice with 30 ml of water and l times with 30 ml of sodium chloride solution.                 Washed. Then, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and then recrystallized with n-hexane and ethyl acetate to give the target compound.                 4.3 g (91% yield) was obtained.

[Analysis value]

m.p: 80-81 ° C

MS (70eV): 194 (M ⁺ )

¹ H NMR (CDCI ₃ ): δ = 2.3 (s, 6H), 3.55 (s, 3H), 5.6 (s, 1H), 6.38 (s, 1H), 6.7-7.0 (m, 3H).

Example 2

Preparation of Methyl 2- (methoxyacetyl) -2- (2,6-dimethylphenyl) -hydrazine-carboxylate (compound of formula (V) above)

2.6-dimethylphenylhydrazine (3 g, 0.022 mol) and potassium carbonate (4.57 g, 0.033 mol) were added to 50 ml of toluene and maintained for 30 minutes while maintaining the temperature of 0 ° C.                 Stirred. Methylchloroformate (2.19 g, 0.023 mol) was added thereto, followed by stirring at 0 ° C to 25 ° C for 1 hour (preparation and purification of Example 1 and                 same). Thus, without adding the compound represented by the above formula (IV), potassium carbonate (4.57 g, 0.024 mol) was added thereto, followed by methoxy                 Acetyl chloride (2.63 g, 0.024 mol) is added. After stirring for 2 hours at room temperature, the reaction was filtered, the filtrate was twice with 30 ml of water,                 Wash once with 30 ml of sodium chloride solution. Thereafter, the resulting solid was dried over anhydrous magnesium sulfate and concentrated under reduced pressure.                 4.lg (yield 70%) was obtained.

[Analysis value]

m.p: 166 to 167 ° C

MS (70eV): 266 (M +)

¹ H NMR (CDCI ₃ ): δ = 2.31 (s, 6H), 3.35 (s, 2H), 3.48 (s, 1H), 3.72 (s, 4H), 4.37 (s, 1H), 6.88 ~ 7.25 (m , 4H)

Example 3

Preparation of N- (methoxyacetyl) -N- (2,6-dimethylphenyl) -3-amino-oxazolidin-2-one (compound of formula (I) above)

Methyl 2- (2,6-dimethylphenyl) -hydrazine-carboxylate (3 g, 0.015 mol) and potassium carbonate (3.2 g, 0.023 mol) prepared in Example 1 were prepared.                 40 ml of N, N-dimethylformamide was added and stirred for 30 minutes while maintaining a temperature of 0 ° C. To this, methoxyacetyl chloride (1.84 g, 0.017 mol) was added.                 After stirring, the mixture was stirred for 2 hours while maintaining the temperature of 0 ° C. Then, potassium carbonate (3.2 g, 0.023 mol) was added thereto, and ethylene oxide (1.02 g, 0.023 mol) was added thereto.                 Add. The reaction mixture is reacted at 0 ° C. to 25 ° C. for 1 hour and then heated at 120 ° C. for 4 hours to terminate the reaction. The reaction is then filtered and                 After the solvent was removed under reduced pressure, the filtrate was added with 100 ml of ethyl acetate, washed twice with 30 ml of water and once with 30 ml of sodium chloride solution.                 Then, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and then recrystallized with petroleum ether and ethyl acetate to give 2.7 g (yield 65%) of the target compound.                 Got it.

[Analysis value]

m.p: 102-103 ° C

MS (70 eV): 278 (M +)

¹ H NMR (CDCI ₃ ): δ = 2.34 (s, 6H), 3.35 (s, 3H), 3.65 (s, 2H), 3.88 (t, 2H), 4.31 (t, 2H), 6.95 ~ 7.30 (m , 3H)

Example 4

Preparation of N- (methoxyacetyl) -N- (2,6-dimethylphenyl) -3-amino-oxazolidin-2-one (compound of formula (I) above)

Methyl 2- (methoxyacetyl) -2- (dimethylphenyl) -hydrazine-carboxylate (3 g, 0.011 mol) prepared in Example 2 above                 Potassium carbonate (2.34 g, 0.017 mole) was added to 30 ml of N, N-dimethylformamide and stirred. Then, ethylene oxide (0.74 g, 0.017 mole) was added thereto at 0 ° C to 5 ° C.                 It is added by syringe (in some cases, a predetermined amount of ethylene oxide may be dissolved in a solvent and then added dropwise with a dropping funnel). The reaction mixture was reacted at 25 ° C. for 30 minutes                 The reaction is then complete by heating at 120 ° C. for 4 hours. Subsequently, the reaction product was filtered, the filtrate was removed under reduced pressure, and then 100 ml of ethyl acetate was added.                 It was added and washed twice with 30 ml of water and once with 300 ml of sodium chloride solution. Then, dried over magnesium sulfate and concentrated under reduced pressure, and then petroleum ether                 As a result of recrystallization using ethyl acetate, 2.19 g (yield 70%) of the title compound was obtained.

[Analysis value]

m.p: 102-103 ° C

MS (70 eV): 278 (M +)

¹ H NMR (CDCI ₃ ): δ = 2.35 (s, 6H), 3.35 (s, 3H), 3.65 (s, 2H), 3.88 (t, 2H), 4.31 (t, 2H), 6.95 ~ 7.30 (m , 3H)

Example 5

Preparation of N- (methoxyacetyl) -N- (2,6-dimethylphenyl) -3-amino-oxazolidin-2-one (compound of formula (I) above)

Methyl 2- (methoxyacetyl) -2- (dimethylphenyl) -hydrazine-carboxylate (0.3 g, 1.12 mmol) and potassium fluorine adsorbed on alumina (KF / A1 ₂ O ₃ , 0.254 g, 1.69 mmol) Into 10 ml of N, N-dimethylformamide and stirred, 1.23 ml (0.054 g; 1.2 mmol) of 4.4 g of ethylene oxide dissolved in 100 ml of toluene was added thereto and heated at 110 ° C. for 1 hour and 30 minutes. The reaction is complete. Subsequently, the solid in the reaction product was filtered and treated in the same manner as in Example 4 to give 0.25 g (yield 80%) of the target compound.

Got it. Analytical values were the same as in Example 4.

Claims (1)

Represented by the following structural formula (I) using 2,6-dimethylphenylhydrazine or its salt represented by the following structural formula (II) as a starting material                 In preparing N- (methoxyacetyl) -N- (2,6-dimethylphenyl) -3-amino-oxazolidin-2-one, 2,6-dimethylphenylhydrazine represented by the following structural formula (II)                 Or an intermediate thereof represented by the following general formula (V) by a known method from a salt thereof, and then reacting ethylene oxide thereto.                 A method for producing N- (methoxyacetyl) -N- (2,6-dimethylphenyl) -3-amino-oxazolidin-2-one represented by the following formula (I).

In the formula (V), R represents a lower alkoxy group having 1 to 5 carbon atoms or a halogen atom.